REFERENCING GUIDLINEcopharm.uobaghdad.edu.iq/wp-content/uploads/sites/... · •Acetaminophen...

REFERENCING

GUIDLINE BY

MAHMOOD SALIH

Referencing Importance

Reliable

Credible

Robustness of Research

Referencing styles

MLA (Modern Language Association)

APA (American Psychology Association)

Chicago

Harvard

Vancouver

In text citation

Human exposure to different types of substance, some of these

substances are cytotoxic like antineoplastic medication in which

cytotoxicity is a major pharmacological action against cancerous cells[1]

Metronidazole is antiprotozoal medication. It used to treat many

pathological conditions like endocarditis, bacterial vaginosis,

giardiasis, trichomoniasis, and amebiasis[7,8]

Reference List (Bibliography)

Article with 1 to 6 authors

Author AA, Author BB, Author CC, Author DD. Title of article.

Abbreviated title of journal. Date of

publication YYYY Mon DD; volume number(issue number):page

numbers.

Example:

Petitti DB, Crooks VC, Buckwalter JG, Chiu V. Blood pressure levels

before dementia. Arch Neurol. 2005 Jan;62(1):112-6.

Reference list (Bibliography) Article with more than 6 authors (list 6 authors only and use et al for

the remaining):

Author AA, Author BB, Author CC, Author DD, Author EE, Author FF, et al. Title of article.

Abbreviated title of journal. Date of publication YYYY Mon

DD;volume number(issue number):page numbers.

Example:

Hallal AH, Amortegui JD, Jeroukhimov IM, Casillas J, Schulman CI,

Manning RJ, et al. Magnetic resonance cholangiopancreatography

accurately detects common bile duct stones in resolving gallstone

pancreatitis. J Am Coll Surg. 2005 Jun;200(6):869-75.

Reference list (Bibliography)

Electronic journal article:

Author AA, Author BB. Title of article. Abbreviated title of Journal [Internet]. Date of publication YYYY MM [cited YYYY Mon

DD];volume number(issue number):page numbers. Available from:

URL

Example:

Stockhausen L, Turale S. An explorative study of Australian nursing

scholars and contemporary scholarship. J Nurs Scholarsh [Internet].

2011 Mar [cited 2013 Feb 19]; 43(1):89-96. Available from:

http://search.proquest.com.ezproxy.lib.monash.edu.au/

docview/858241255?accountid=12528


Print book:

Author AA. Title of book. # edition [if not first]. Place of Publication:

Publisher; Year of publication. Pagination.

Example:

Carlson BM. Human embryology and developmental biology. 4th ed.

St. Louis: Mosby; 2009. 541 p.


Chapter in a book:

Author AA, Author BB. Title of book. # edition. Place of Publication:

Publisher; Year of publication. Chapter number, Chapter title; p.

[page numbers of chapter].

Example:

Speroff L, Fritz MA. Clinical gynecologic endocrinology and infertility.

7th ed. Philadelphia: Lippincott Williams & Wilkins; c2005. Chapter 29,

Endometriosis; p. 1103-33.


Electronic book:

Author AA. Title of web page [Internet]. Place of Publication:

Sponsor of Website/Publisher; Year published [cited YYYY Mon DD].

Number of pages. Available from: URL DOI: (if available).

Example:

Shreeve DF. Reactive attachment disorder: a case-based approach

[Internet]. New York: Springer; 2012 [cited 2012 Nov 2]. 85 p. Available

from: http://ezproxy.lib.monash.edu.au/

login?url=http://dx.doi.org/10.1007/978-1-4614-1647-0


Edited Book:

Editor AA, Editor BB, editors. Title of book. # edition [if not first]. Place

of Publication: Publisher; Year. Pagination.

Example:

O'Campo P, Dunn JR, editors. Rethinking social epidemiology: towards

a science of change. Dordrecht: Springer; 2012. 348 p.


Website (trusted)

Website name, name of topic[format] year [cited date] available

online from URL.

Example

World Health Organization. Drinking water [Internet]. Geneva: World

Health Organization; 2015 Jun [cited 2015 Jul 20]. Available from:

http://www.who.int/mediacentre/factsheets/fs391/en/

Further information

Trusted references

https://guides.library.uwa.edu.au/vancouver

https://guides.library.uwa.edu.au/vancouver

Any questions

Thanks for Listening

Hasan Alhaddad, MSc

Department of Pharmacology and Toxicology

College of Pharmacy/ University of Baghdad

2014

Non-steroidal anti-inflammatory drugs (NSAIDs)

• Non-steroidal anti-inflammatory drugs (NSAIDs) • Analgesic, anti-inflammatory, and antipyretic • OTC drugs• The most widely used of all drugs• Used to relieve mild to moderate pain

• Gastrointestinal toxicity including bleeding ulcer• Risk of cardiovascular events• Kidney damage

NSAID overdose

• Symptoms of NSAID overdose are usually mild• Gastrointestinal upset, abdominal pain, vomiting and diarrhea• 5% to 10% of patients experience convulsions. Metabolic acidosis is

uncommon • Rarely, coma, prolonged seizures, apnea, bradycardia, renal failure

and death may occur

NSAID overdose

Acetaminophen

• Acetaminophen (paracetamol) is not a NSAID, but a distinct analgesic and fever reducing drug with a similarly broad usage

• Most commonly used OTC analgesic & also most common over dose leading to hospital • Overdose is the leading cause of acute liver failure in the developed

world • 56,000 emergency room visits, 26,000 hospitalizations, and 458

deaths due to acute liver failure• Kidney toxicity

FDA: combination prescription pain relievers that contain more than 325 mg of acetaminophen per tablet, capsule, or other dosage unit should no longer

be prescribed because of a risk of liver damage

Toxicokinetics

• Relatively safe• Rapid oral abs with peak levels at 1-2hrs for tablets (30mins

for elixir)• 20% is metabolized by gut wall, rest by the liver • Elimination T½=~2hrs, ≥4hrs in over dose where• LETHAL DOSE 15-25g• Liver damage severe with >10g doses; Children: 150 mg/kg

Acetaminophen

60% glucuronide conjugates30% to sulfate conjugates

4% is metabolized by the cytochrome P450 mixed-function oxidase system (3A4 at low doses; 2E1 predominantly at high doses) to the potentially toxic reactive intermediate N-acetyl-p-benzoquinoneimine

(NAPQI).

conjugated with glutathione to form nontoxic cysteine and mercapturic acid conjugates

Metabolism

Acetaminophen

Acetaminophen

ToxicityNAPQI induces oxidation of enzymes which alter normal cell functions and impairs cell defenses against endogenous reactive oxygen species

Hepatic toxicity becomes evident only when hepatic GSH falls to 30% of baselineTherapeutic Dose: 10 to 15mg/kgToxic Dose: 150 mg/kg

Factors that may predispose patients to hepatotoxicity• Increased frequency and duration of acetaminophen dosing• Increased capacity for CYP2E1 activation to NAPQI• Decreased GSH availability• Decreased capacity for glucuronidation and sulfation• Alcohol

Acetaminophen Level Result Interpretation

10-20 mcg/mL Therapeutic levels

Less than 150 mcg/mL 4 hours after ingestion

Low risk of liver damage

Greater than 200 mcg/mL 4 hours after ingestion OrGreater than 50 mcg/mL 12 hours after ingestion

Associated with toxicity and liver damage

Acetaminophen

Stage I toxicityWith in 24 hours, No hepatic injury, asymptomatic, N/V/abdominal pain

Stage II toxicity24 to 72hours, right upper quadrant abdominal pain, anorexia, N/V,

Tachycardia and hypotension , Raised liver function test

Stage III toxicity72 to 96 hours, N/V/abdominal pain, Maximal liver injury (jaundice, coagulopathy,

hypoglycemia, and hepatic encephalopathy), Acute renal failure,Death from multiorgan failure

Stage IV toxicityThe recovery phase, Patients who survive stage III

Laboratory tests

• Serum acetaminophen levels• Management is dependent on

the serum acetaminophen level and the time of ingestion

• Rumack/Matthew nomogram• Paracetamol concentrations

taken between 4 and 24 hours after ingestion

Laboratory tests• Liver function tests

• alanine aminotransferase [ALT]• aspartate aminotransferase [AST]• bilirubin [total and fractionated]• alkaline phosphatase

• Prothrombin time (PT) with international normalized ratio (INR)• Glucose• Renal function studies (electrolytes, BUN, creatinine)• ECG• Lipase and amylase (in patients with abdominal pain)• Other tests to consider

• Serum salicylate level: in unconscious patients or those in whom there is a suspicion of co-ingestion of salicylates

• Urine drug screen: may be used in patients who are unconscious to determine if other substances have been taken

Special clinical considerations

• Glutathione deficiency• people with acute or chronic starvation• Eating disorders (e.g., anorexia or bulimia)• Patients with chronic debilitating illnesses (e.g., cystic fibrosis, AIDS,

alcoholism, or hepatitis C)

• Prior medications• Long-term treatment with CYP 450 inductors (e.g., carbamazepine, rifampicin)• Long standing alcohol

• Children

Out of hospital treatment

• Activated charcoal, with in the first hour after overdose• Ipecac and Lavage might be used with in 2 hours of ingestion

(not common)• Antiemetics are used to relieve nausea and vomiting, which

can result from both acetaminophen toxicity and from Activated charcoal and oral N-acetylcysteine administration

N-acetylcysteine

• The mainstay of treatment for paracetamol toxicity• Antidote for paracetamol• As early as possible• Is a sulfhydryl donor, replenishes glutathione stores• Loading dose of 140 mg/kg then 70 mg/kg given every 4 hours• Total treatment duration of 72 hours• Should be given even if the history is unclear but a potentially

toxic acetaminophen ingestion is suspected. NAC should be administered while awaiting a serum Acetaminophen level if the patient presents close to or later than 8 hours after an acute ingestion

• N-acetylcysteine• Sulphurous compound:

• Causes vomiting when given by mouth or nausea when given intravenously

• Asthma, family history of drug allergy, and women• Treated by interrupting the acetylcysteine infusion and providing

symptomatic relief with an antihistamine such as chlorpheniramine and nebulized salbutamol

• Liver transplantation, patients with severe hepatotoxicity and potential to progress to hepatic failure• Metabolic acidosis• Renal failure• Coagulopathy• Encephalopathy

Case studyA 21-year-old woman was brought to the emergency department

(ED) by her friend when he learned that she ingested approximately 30 (325-mg) acetaminophen tablets in an attempted suicide. He was unaware of any previous significant medical or psychiatric illness but reported that she was seen in another ED several days earlier for persistent headaches. He said that she did not abuse alcohol or any other drugs.

The patient was able to provide a history and admitted to taking approximately 30 tablets approximately 3 hours before coming to the hospital because she wanted to kill herself. Shortly after taking the tablets she developed a bad stomach ache, felt extremely nauseated, and vomited once. She denied taking any other medications or alcohol in the suicide attempt.

ACETAMINOPHEN

SALICYLATES

• Salicylate-containing medications have been widely used in the world• Aspirin• Topical products containing salicylates, such as Ben-Gay, salicylic acid,

and oil of wintergreen or methyl salicylate

• Continues to be responsible for a significant number of cases of morbidity and mortality every year

• Salicylism, acute or chronic poisoning

OTC Analgesic Exposures 64% acetaminophen

19% ibuprofen17% aspirin

OTC Analgesic Fatalities 62% aspirin

34% acetaminophen04% ibuprofen

Toxic dose• Less than 150 mg/kg - no toxicity to mild toxicity• 150-300 mg/kg – Mild to moderate toxicity• 301-500 mg/kg - Serious toxicity• Greater than 500 mg/kg - Potentially lethal toxicity

Toxicokinetics• Aspirin is a weak acid (pKa = 3.5)• Rapidly absorbed (peak ~1hr or 4-6 if enteric coated) • ~5-10% is excreted unchanged as salicylic acid• ~90% oxidation, glycine conjugation, and glucoronide conjugation• Therapeutic T½=2-4.5hr, but in over dose T½~18-36hr

SALICYLATES

Toxic mechanismsAcid-base, fluid, and electrolyte abnormalities

SALICYLATES

Phase 1 hyperventilation

resulting from direct respiratory center

stimulation, respiratory alkalosis and

compensatory alkalurialast as long as 12 hours

Phase 3 Dehydration,

hypokalemia, and fever

4-6 hours after ingestion in a young infant or 24 hours or

more in adults

phase 2Metabolic acidosis,interrupts aerobic respiration, Krebs cycle and lactate

accomulationlast 12-24 hours

Metabolic acidosisAffect TCA (↑glucose utilization, ↑lactic acid) & Urea

(↑ammonia) Cycles

Glucose metabolismHypoglycemia, ↑tissue glycolysis, ↓glucose synthesis

Other effectsInhibit Vit K dependent factors II, VII, IX & X →↑INR

Toxic mechanisms

Clinical features • Hyperthermia is an indication of severe toxicity

• Acute intoxication • Gastric effects: N & V, Gastritis • CNS effects: N & V, tinnitus, confusion, hallucinations, seizures • Metabolic effects: Hyperventilation, Acid-base disturbance (respiratory

alkalosis, metabolic acidosis), dehydration, electrolyte disturbances, fever

• Chronic intoxication• More common in elderly• Lower GI symptoms & higher non-specific neuro symptoms• Confusion, delirium, dehydration, metabolic acidosis, cerebral oedema

SALICYLATES

Lab tests• Salicylate level

• If enteric coated preparations, serial salicylate levels (2 hourly)• 15-30 mg/dL: therapeutic level • Higher than 40-50 mg/dL: symptomatic• Above 100 mg/dL: life-threatening toxicity

• Arterial blood gas (ABG)• Respiratory alkalosis• Metabolic acidosis

• Electrolytes, BUN/creatinine, glucose• Anion-gap metabolic acidosis• Hypokalemia• Baseline renal function

• Imaging studies• Abdominal radiograph• Computed tomography (CT) scanning of the abdomen• Endoscopy

SALICYLATES

Management

• Asymptomatic• Charcoal 1g/kg• I.V. bicarbonate infusion 1mmol/kg/hr to correct any acidosis (pH <7.3)

• Symptomatic• Charcoal 1g/kg unless altered conscious state • Whole-bowel irrigation, hemodialysis • I.V. fluid resuscitation to correct dehydration (use N. Saline)• I.V. bicarbonate infusion 1mmol/kg/hr, after initial slow bolus of

2mmol/kg, (Alkalization, urine pH >7.5)• Potassium replacement (20–40 mEq KCl per liter)• Respiratory support ± haemodialysis in case of convulsion and coma• STABILIZATION THERAPY

SALICYLATES

Case studyA 22-years-old woman came to the emergency department

complaining of abdominal pain, nausea, and vomiting. She had a history of depression but stated that she currently was not being treated by a psychiatrist or taking any psychiatric medications. Upon further questioning, the patient said that 6 hours earlier she had been severely depressed and had ingested at least half a bottle of aspirin tablets in a suicide attempt, after which she vomited once. She denied tinnitus but said that she was short of breath. She denied significant past medical or surgical problems.

SALICYLATES

Digitalis toxicity

Hasan Alhaddad, MSc


College of Pharmacy/ University of Baghdad

2014

Cardiac glycosides

Digitalis is the oldest compound in cardiovascular medicine

Cardiac glycosides include digoxin, digitoxin, digitalis and

ouabain

+ve inotropic, -ve chronotropic

Heart failure, Atrial fibrillation, Atrial flutter

Low TI

Mechanism Of Pharmacological Action

Potent inhibitors of cellular Na+/K+-ATPase This ion transport system moves 3 sodium ions out of the cell

and brings 2 potassium ions into the cell

Necessary for cell survival

Subsequent inhibit the Na+-Ca++ exchanger

Three sodium ions are exchanged for each calcium

An increase in intracellular sodium concentration competes for calcium through this exchange mechanism leading to an increase in intracellular calcium concentration, leading to increases contractility (inotropy)

Increase vagal efferent activity to the heart, reduces sinoatrial firing rate (decreases heart rate; negative

chronotropy) and reduces conduction velocity of electrical impulses through the atrioventricular node (negative dromotropy)

Mechanism Of Pharmacological Action

Kinetics

25%

Protein

Binding

Age, Renal, and

cardiac

function

dependent

Approximately

38 Hours (parent

drug)

Half Life

Oral: 1-3 hours

Distribution

phase: 6-8 hours

Steady state:

7-10 Days

Time to peak

(serum)

5-7 L/kg

Volume of

Distribution

Electrocardiography (ECG)

Digitalis toxicity

life-threatening condition, 1,500/year

In 2011, there were 2,513 cases involving cardiac glycosides reported to U.S. poison control centers. Of these, 90 experienced major effects (i.e, life threatening resulting in prolonged hospitalization) and 26 died

Low TI Therapeutic levels are 0.6 to 2 ng/mL

levels of toxicity between therapeutic and toxic ranges

Acute toxicity cardiac effects

nausea and vomiting

Chronic toxicity cardiac effects

nonspecific symptoms include fatigue, malaise, and visual disturbances

Digitalis toxicity

Causes

High levels of digitalis in the body (over dose)

Accumulation during chronic treatment

Decreased tolerance to the drug, have normal levels of

digitalis in blood

Risk factors Electrolyte Imbalance

Potassium loss (thiazide)

Low levels of magnesium

Hypercalcemia

Quinidine, flecainide, verapamil, amiodarone.

Kidney failure and dehydration

Signs/symptoms of acute toxicity

Gastrointestinal

nausea, vomiting, abdominal

pain

Neurological

weakness, confusion,

Photophobia

Electrolyte

Hyperkalemia

(> 5.5 mEq/L is a poor

prognostic sign)

Cardiac

Palpitations, bradycardia, heart

block, several types of

arrhythmias, and Shortness of

breath

Less than that of acute digoxin

toxicity (nausea, anorexia)

confusion, drowsiness,

headache, hallucinations

sensitivity to light, yellow halos

around lights, blurred vision

Signs/symptoms of chronic toxicity

Gastrointestinal Neurological

Visual

Diagnosis

Serum digoxin level

Electrolytes

Renal function studies

ECG

Diagnosis

Serum digoxin level

Toxicity begins >2.0 ng/mL

May be misleading in the acutely poisoned patient

False-negative assay results may occur with acute

ingestion of non-digoxin cardiac glycosides (eg,

foxglove or oleander)

Digoxin’s long distribution phase results in high serum

levels for 6-10 hours prior to completed tissue

distribution

Diagnosis

Electrolytes

Hyperkalemia

Chronic toxicity: hypokalemia and hypomagnesemia

Kidney function tests

BUN

Creatinine

Diagnosis ECG

May cause almost any dysrhythmia

atrial tachycardia with a 2:1 conduction

bidirectional ventricular tachycardia

atrial fibrillation with a slow ventricular response

atrial tachycardia

with block

Sinus rhythm with

frequent PVCs in a

pattern of ventricular

bigeminy

Treatments

Decontamination/enhanced elimination

Enhanced elimination

(dialysis, hemoperfusion)

does not effectively

remove digoxin due to large volume of

distribution and relatively

high protein binding

For acute overdose:

Activated charcoal,

multiple dose activated

charcoal, gastric lavage

Treatments

Digoxin immune Fab (ovine)

• Antidote, highly effective in treating life-

threatening signs of digoxin toxicity such as

hyperkalemia, hemodynamic instability,

and arrhythmias

• Primary treatment of digoxin toxicity

• Indications:

• Ingestion of 10 mg of digitalis (in

children, 4 mg)

• Serum digoxin level greater than 8

ng/mL in adults at steady state

• Hyperkalemia (greater than 5 mEq/L)

• Altered mental status

• Rapidly progressive signs and

symptoms of toxicity

DigiFab (40 mg of Fab), binds 0.5 mg digoxin

30 minute slow IV infusion

Acute ingestion of unknown amounts and serum concentration of digoxin:

20 vials of Digoxin immune fab (ovine)

Can split dose into 10 vials followed by another 10 vials to avoid a febrile reaction

Chronic ingestion unknown serum digoxin concentration

6 Vials of Digoxin immune fab (ovine) in adults and Children > 20 Kg

1 Vial of Digoxin immune fab (ovine) in infants and Children < 20 Kg

Treatments

Treatments

For known amounts of digoxin

Digoxin ingested (mg) X 1.6 Dose In Vials =

Round up to the nearest vial

Treatments

Round up to the nearest vial

For known digoxin serum concentration

(Serum Digoxin ng/mL) x Weight (kg)

Dose In Vials =100

Treatments

Digoxin immune Fab

Adverse Effects

Digitalis withdrawal: exacerbation of HF, rapid ventricular

response and postural hypotension

Hypokalemia

Phlebitis

Fever, May occur with doses above 10 vials

Warning

Patients who require digoxin’s inotropic action may deteriorate

secondary to the withdrawal of digoxin

Additional inotropic support may be required for these patients

(e.g, dopamine, dobutamine or vasodilators)

Treatments

Electrolyte imbalance

Hyperkalemia, use insulin plus glucose, and sodium bicarbonate if the

patient is acidotic

Hemodialysis may be necessary for uncontrolled hyperkalemia

Correct hypokalemia (usually in chronic intoxication)

Concomitant hypomagnesemia may result in refractory hypokalemia

Dysrhythmias

Short-acting beta blockers (eg, esmolol) may be helpful for

supraventricular tachyarrhythmias with rapid ventricular rates, but

may precipitate advanced or complete AV block

Phenytoin and lidocaine are useful for ventricular tachycardia

Phenytoin can suppress digitalis-induced tachydysrhythmias

Atropine has proved helpful in reversing severe sinus bradycardia

Magnesium sulfate may terminate dysrhythmias

Digoxin Toxicity: Case Study76 year old woman with history of atrial fibrillation, hypertension, renal

impairment, breast cancer, osteoarthritis. Stroke 1 month prior to

admission.

Medications: digoxin 250 mcg once daily, amlodipine, lisinopril,

indapamide

SR, simvastatin, clopidogrel, bisoprolol, omeprazole, erythromycin

Presents with nausea, vomiting, change in vision, lethargy

VS: BP “normal”; HR 35-38 bpm

Labs

Digoxin levels: prior to admission: 3.4 ng/mL (0.8-2 ng/mL normal range for this

lab)

On admission: 2.9 ng/mL

Increased digoxin dose from 125 mcg/day to 250

mcg/day 28 days ago

Summary: elderly patient with renal impairment,

signs/symptoms of (chronic) digoxin poisoning with

elevated digoxin level

Potential drug interactions:

(Ca+2 channel

blocker)

can increase

digoxin level and

enhance digoxin

AV blocking effect

Amlodipine

(macrolide

antibiotic) can

increase digoxin

level

Erythromycin

(ß blocker)

can enhance

digoxin’s

bradycardic effect

Bisoprolol

Digoxin Toxicity: Case Study


Received digoxin-specific antibody fragments (Fab)

(Serum Digoxin ng/mL) x (Weight in kg)

Fab Dose In Vials =100

Weight 108 kgDigoxin level: 2.9

ng/mL

3 vials administered


6 hours post digoxin Fab infusion: digoxin 1.9 ng/mL

At discharge (91 hours post digoxin Fab infusion): digoxin

1 ng/mL, HR 65 bpm, digoxin toxicity signs/symptoms

resolved

Monitoring

HR: improved (35-38 bpm to 65 bpm

at discharge)

BP: remained stable

EKG: unchanged from baseline

(atrial fibrillation)

K+ not provided in this report

(although this was a chronic toxicity

not acute)


Approaches to digoxin

poisoning in the chronically

poisoned patient will

depend on the status of the

patient (signs/symptoms,

age, renal function,

cardiac status)

This was an elderly patient

with impaired renal function

who clearly had digoxin

toxicity and an elevated

level.

The clinical decision was

made to treat promptly

with digoxin Fab rather than

prolong her clinical course.

TOXICITIES FROM DRUGS OF ABUSE

Hasan Alhaddad, MSC


College of Pharmacy/ University of Baghdad, 2014

DRUGS OF ABUSE

• People abuse (misuse) substances such as drugs, alcohol, and tobacco for varied and complicated reasons

• Many first try drugs out of curiosity, to have a good time, because friends are doing it, or in an effort to improve athletic performance or ease another problem, such as stress, anxiety, or depression

• Society pays a significant cost• Direct damage to health by substance abuse and its link to

physical trauma

• Strong connection between crime and drug dependence and abuse

• Many street drugs have no therapeutic benefits. Any use of these drugs is a form of drug abuse

DRUGS OF ABUSE

Types of Abused Drugs

• Depressants: depress functions of central nervous

system, cause calm and bring about sleep (alcohol,

barbituates). Tranquilizers are depressants

• Stimulants: increase alertness and activity (cocaine,

amphetamines)

• Steroids: promote muscle growth (androgen,

testosterone, anabolic steroids)

DRUGS OF ABUSE

AlcoholBeer, Liquor, gin

Calming and drowsy

effects

High potential for

abuse and addiction

NicotineCigarettes, Cigars, Snuff

Addictive substance of

tobacco

Stimulant or sedative

30% of total cancers,

CVD, Chronic bronchitis

DRUGS OF ABUSE

HeroinSmack, Junk, Black tar

Most widely abused opiate,

extremely addictive

No medical use

Rush of pleasure followed by drowsiness and N/V

CocaineCoke, Crack

Powerful stimulant,

Increase energy and

decrease appetite

Heart disturbances,

strokes, and respiratory

failure

DRUGS OF ABUSE

MarijuanaWeed, Hash, Pot

Cannabis Sativa

Most common drug used

Euphoria then depression

Impairs memory and

attention, and slows

reaction time

HallucinogensMescaline

LSD (Lysergic Acid

Diethylamide)

Hallucination:distortion

of perception of reality

and time

Mydriases, fever, and

tremors

DRUGS OF ABUSE

MethamphetamineSpeed, Ice

Strong stimulant, very addictiveBrain toxicity, fever, and convulsion

Chronically: violent behavior,

insomnia, and anxiety

DRUGS OF ABUSEMDMA

Ecstacy, Love drugMethylenedioxymethamoh

etamine

Stimulant and hallucinogen

Chills and muscle crumping

Overdose: unconsciousness

and convulsionsDate Rape Drugs

Colorless and tasteless, victims

are unable to resist assault and

recall what happened next day

GHB: depressant has relaxing

effect (party goers) and muscle

growth (body builders), it cause

coma and death at high dose

Rohypnol (flunitrazepam):

depressant drug

DRUGS OF ABUSE

InhalantsGlue, Sniff

Household products

Feeling high

Permanent brain

damage and death

Anabolic steroidsSteroids, Jym candiesMale sex hormones

analogues

Strokes, hair loss and acne

Psychological

dependence

Dissociative drugs

Ketamine,Detromethorphan,

and PCP


• Toxicity caused by drugs of abuse is a frequent reason for

presentation to hospital

• Associated with toxic effects on almost every system of the

organism

• Stimulants produce excitement, increased heart rate, and rapid

breathing, while depressants do the opposite

• Drug overdose symptoms vary widely depending on the specific

drug used, but may include:• Abnormal pupil size

• Agitation

• Convulsions

• Death

• Hallucinations

• Nausea and vomiting

• Unconsciousness (coma)


Opioids• Heroin use remains a substantial public health problem and deaths

from respiratory depression and cardiovascular collapse following

overdose

• Naloxone is still the mainstay of therapy for severe opiate toxicity

• Substitution therapy with methadone or buprenorphine

• The morbidity and mortality associated with cocaine use is high: in the USA, 40% of emergency department visits due to illicit drugs

involve cocaine

• Acute coronary insufficiency and arrhythmias are common toxicities


Cannabis• Cannabis ( marijuana, hashish) is the most widely used recreational

agent

• Although not often associated with acute toxicity requiring hospital

admission, there is increasing recognition of its cardiovascular,

respiratory and central effects

• Respiratory effects, tachycardia and hypotension or hypertension,

and psychosis


Ecstasy• Acute effects are attributable to hyper-stimulation of the nervous

systems via increased release and inhibited re-uptake of serotonin,

norepinephrine and dopamine

• Hyperpyrexia, altered consciousness, disseminated intravascular

coagulation, multi-organ failure and death

Inhalants• Inhale the toxic chemicals of common products, the

concentration of the fumes can be thousand times greater than

the maximum permitted in industrial settings

• Experimentation, Cost effectiveness, and Easy availability• Hallucinations, loss of self-control, violent behavior, nausea,

unconsciousness or even death


Elvis Presley died of a cardiac arrhythmia; legend has it that he was seated on

the toilet at the time. His death was liked to many different drugs. One report,

found fourteen different drugs in Elvis' system, ten in significant quantity

Michael Jackson died of acute propofol

and benzodiazepine intoxication after

suffering cardiac arrest at his home

TOXICITIES FROM ANTIDEPRESSANTS

Hasan Alhaddad, MSc


College of Pharmacy/ University of Baghdad, 2014

ANTI-DEPRESSANT DRUGS

• Drugs used for the treatment of:

• Major depressive disorder

• Dysthymia

• Anxiety disorders

• Obsessive compulsive disorder

• Eating disorders, chronic pain, neuropathic pain and, in some

cases, dysmenorrhoea, snoring, migraines, attention-deficit

hyperactivity disorder (ADHD), substance abuse and sleep

disorders

• The pathophysiology of depression is complex and not

completely understood

• Monoamine hypothesis

Normal

Depression



• Depression knows no age boundaries

• 10% to 15% of children and adolescents have some symptoms of

depression

• Major depression strikes about 1 in 12 adolescents

• Among them, 1 in 14 will commit suicide as a young adult

• Depression is the most frequent psychiatric disorder in

people dying by suicide

• Self-poisoning is a common method of suicide, especially in

women

• Antidepressants are frequently used for self-poisoning


• Antidepressant Drugs and the Food and Drug Administration

Black Box Warning, 2004


• 4 major classes of antidepressant drugs

Monoamine oxidase inhibitorsUsed only to treat depression which is

resistant to the other classes of

antidepressants because of their serious

toxicity

Phenlzine, Tranylcypromine, and

Isocarboxazid

Cyclic AntidepressantsNeuralgic pain, migraines, enuresis, and

attention deficit hyperactivity disorder

NE and serotonin reuptake inhibition,

anti-muscarinic activity

Imipramine, amitriptyline, maprotiline

and amoxapine

Selective Serotonin Reuptake

Inhibitors SSRIobsessive-compulsive disorders, panic

disorder, alcoholism, obesity, migraine

headache, and chronic pain syndromes

Citalopram, and Fluoxetine

Less side effects

Atypical AntidepressantsSerotonin reuptake inhibition with other

neurotransmitter activity

Venlafaxine, Duloxetine, and Bupropion

MAO INHIBITORS TOXICITY

• The clinical toxicity of MAOIs falls into 3 clinical syndromes

Acute toxicity

from overdose-Symptoms may be delayed 6 to 24

hours-Sympathetic hyperactivitywhich is followed by cardiovascular collapse-Hyperthermia, seizures, and hypertension-Renal failure and dehydration

Serotonin syndrome-Life threatening complication

of antidepressant

-Altered mental status,

increased neuromuscular

tone, and autonomic

excitation

-Prolonged duration of risk for the developmentof the syndrome after the discontinuation of the drug due to long duration of action-“washout” period of at least 2

weeks

Hypertensive crises-Food-drug and drug-drug

interactions

-Pharmacologically active

dietary amines (eg, tyramine)

are ingested by Patients

-Indirectly acting

sympathomimetic

agents (eg, cocaine,

amphetamine)

-Hypertension and

tachycardia, headache,

and altered mental status

-Usually last only several hours

compared to MAOI

overdoses in which symptoms

can last several days

CYCLIC ANTIDEPRESSANTS TOXICITY

• Acute cardiovascular toxicity is primarily responsible for the

morbidity and mortality

• Sinus tachycardia is the most common dysrhythmia

• Refractory hypotension is probably the most common cause of

death from CA overdose (Na channel blockade)

• Seizures and altered mental status are the primary manifestations

of CNS toxicity

• Anticholinergic effects• Dilated Pupils, dry mouth, dry flushed skin, hyperthermia, urinary retention

CYCLIC ANTIDEPRESSANTS TOXICITY

Electrocardiogram of

patient with tricyclic

antidepressant toxicity. QRS

interval, 130 milliseconds;

R wave in lead aVR, 4 mm

(arrow)

SSRI TOXICITY

• Wide therapeutic index

• Mild or no symptoms after an overdose

• Acute signs and symptoms include nausea, vomiting, dizziness,

blurred vision, tachycardia, and CNS depression

• Serotonin Syndrome “serotonin toxicity”• Uncommon

• Clinical manifestations may range from mild confusion, tachycardia, and

tremor to coma, hyperthermia, and muscular rigidity

• Combination of serotonergic agents

ATYPICAL ANTIDEPRESSANTS TOXICITY

• Each present unique toxicities in overdose

DIAGNOSTIC TESTING

• There are no specific diagnostic tests

• Electrocardiogram (ECG), specially for CAs

• Antidepressant serum concentrations are not available immediately

in most hospital settings

TREATMENTS

• Airway, ventilation, and circulation should be assessed and managed

• Activated charcoal

• Seizures

• Benzodiazepines

• Phenobarbital

• Hypertension associated with MAOI toxicity

• Nitroprusside continuous infusion

• Phentolamine mesylate

• β-adrenergic antagonists C/I: (potent interaction with MAOIs, leading to a greater

than expected drop in blood pressure and dizziness).

• α-methyldopa are C/I:( aromatic L-amino acid decarboxylase, which converts L-

DOPA into dopamine. Dopamine is a precursor

for norepinephrine (noradrenaline) and subsequently epinephrine (adrenaline)

TREATMENTS CONT.

• Neuromuscular rigidity (MAOI toxicity, serotonin syndrome)

• Benzodiazepines (Lorazepam and Diazepam)

• Cyproheptadine

• Wide-complex dysrhythmias• NaHCO3 boluses

***proposed mechanisms of action of sodium bicarbonate include: (1) treatment of drug overdoses whereby the offending agent has sodium channel blocking properties; (2) urinary and serum alkalinization to enhance the elimination of drugs by “ion trapping” and minimize drug distribution, respectively; (3) promoting the solubility of drugs or toxins that may otherwise precipitate in the kidney resulting in renal failure; and (4) neutralization of toxins that produce severe acidemia.

• Lidocaine

• Magnesium sulfate

Dorothy Dandridge, 1965

Imipramine overdoseThe first African-American to be

nominated for an Academy Award for

Best Actress, the 42-year-old Dandridge

was found dead by her manager from

what was diagnosed as “acute drug

intoxication.” Her death was ruled to be

due to an accidental overdose of

Tofranil, an antidepressant that she took

for what today might be diagnosed as

bipolar disorder

Oscar-winning actor and comedian

Robin Williams was found hanged

Williams had reportedly been battling

depression, according to a statement

from his press representative

Hasan Alhaddad, MSc


College of Pharmacy/ University of Baghdad 2014

Food poisoning (foodborne illness) Illness caused by eating contaminated food

Infectious organisms (bacteria, viruses and parasites) or their toxins are the most common causes of food poisoning

Contamination of food may occur at any point of processing or production, or at home if food is incorrectly handled or cooked

Cross-contamination is often the cause

Most often, food poisoning is mild and resolves without treatment, however, some people need to go to the hospital

It is more commonly occurred after eating at picnics, school cafeterias, large social functions, or restaurants

Food poisoning is a common, costly -yet preventable- public health problem

WHO estimates that food and waterborne diarrheal diseases kill about 2.2 million people annually, 1.9 million of them are children

In USA

Each year roughly 1 in 6 Americans (or 48 million people) get sick,

128,000 are hospitalized

3,000 die of foodborne diseases

Yearly loss of up to $17 billion

In UK

Foodborne diseases affect around a million people annually

20,000 people receive hospital treatment

500 deaths

Cost nearly £1.5 billion

In Iraq, although Food Poisoning outbreaks occurred frequently, they are rarely notified, investigated or documented

A mass outbreak of organo-mercury poisoning due to consumption of treated grain by farmers and their families occurred in Iraq in 1971-72, leading to admission of 6,530 cases, and 459 deaths

In 2013, an outbreak of Food Poisoning involving more than 100 persons attending a restaurant in Tikrit. One of them was dead

Staphylococcus aureus and Salmonella typhimurium were the responsible pathogens

Contaminated food stuff and un-hygenic food-handlers practices were the source

Many bacterial, viral or parasitic agents, and chemicals cause food poisoning

Contaminant Onset Foods affected and means of transmission

Campylobacter 2 to 5

days

Meat and poultry, Contamination during processing -

feces contact meat surfaces. Milk and water

Clostridium botulinum 12 to 72

hours

Improperly canned commercial foods, smoked or salted

fish, potatoes baked in aluminum foil

Clostridium perfringens 8 to 16

hours

Meats, stews and gravies

Escherichia coli

O157:H7

1 to 8

days

Beef contaminated with feces during slaughter. Milk and

contaminated water

Staphylococcus aureus 1 to 6

hours

Meats and prepared salads. Spread by hand contact,

coughing and sneezing

Hepatitis A 28 days Raw, ready-to-eat produce. Spread by an infected food

handler

Listeria 9 to 48

hours

Hot dogs, luncheon meats, unpasteurized milk and

cheeses. Spread through contaminated soil and water

Other causative agents:

Giardia lamblia

Noroviruses (Norwalk-like viruses)

Rotavirus

Salmonella

Shigella

Vibrio vulnificus

Norovirus is a contagious virus responsible for more than half of

food poisoning cases

Salmonella is the most common pathogens that caused

hospitalizations

Escherichia Coli found in the intestines of all humans and animals.

Certain strains can cause illness when ingested. The bacteria may

contaminate meat during processing. It can also seep into foods

that are not prepared safely

Toxins There are many toxins that can cause food poisoning. Some are

produced by bacteria on or in food and others are produced by

plants and animals/fish or other organisms that are ingested.

There are many plants and animals/fish that can be poisonous

under certain conditions but they are encountered infrequently or

under special conditions

Bacteria Plants Animals/fish/other

enterotoxins Mushroom toxins Scombroid toxin

exotoxins Belladona Ciguatera toxin

cytotoxins Ricin Sasitoxin

Neurotoxins Hemlock Tetrodotoxin

Chemicals

Certain chemicals are considered toxins that can cause food poisoning

Mercury, found in drinking water and in fish such as tuna and marlin

Other examples of chemicals that can be toxic if enough contaminates

food and water are pesticides, polychlorinated biphenyls, and lead

Food allergy

Is an abnormal response to a food triggered by body's immune system

Some foods, such as nuts, milk, eggs, or seafood, can cause allergic

reactions in people with food allergies

Treatments ??

Start within hours after eating the contaminated food, or they may begin days or even weeks later

Sickness caused by food poisoning generally lasts from a few hours to several days

Common signs and symptoms

Nausea, Vomiting, Watery diarrhea, Abdominal pain and cramps, Fever

Specific bacteria may cause these signs and symptoms

Clostridium botulinum: weakness, blurred vision, difficulty speaking and swallowing, respiratory failure and death

Salmonella spp., Shigella spp., and Campylobacter: fever, chills and bloody diarrhea

Escherichia coli (E. coli): hemorrhagic colitis (diarrhea with very little stool and large amounts of blood), occurring up to 3 days after eating contaminated food

Mushroom poisoning: stomach upset, delirium (confusion), vision difficulties, heart muscle problems, kidney failure, death of liver tissue, and death if left untreated

Older adults

Immune system may not respond as quickly and as effectively to infectious

organisms compared to youngers

Pregnant women

Changes in metabolism and circulation may increase the risk of food

poisoning

Infants and young children

Immune systems have not fully developed

People with chronic disease

Reduces the immune response

Diabetes, liver disease, AIDS, and chemotherapy or radiation therapy for

cancer

History Duration, Symptoms , Kind of food

Physical exam Signs of dehydration

Diagnostic tests, to identify the infectious organism Blood test

Stool culture

It is necessary that large numbers of the organisms be present in a food for it to be hazardous The laboratory reports the number of organisms present per gram of food

For Staphylococcus aureus, the current method is to screen for enterotoxin first, culturing for the organism will occur only if necessary

Other bacteria, any number of organisms present in a ready-to-eat food may be significant For these kinds of agents, the laboratory reports their presence or absence.

Their presence in a ready-to-eat food should be considered significant

Treatment for food poisoning typically depends on the source of the illness, if known, and the severity of symptoms

Lavage and activated charcoal

Control nausea and vomiting

Replacing fluids and electrolytes (such as sodium, potassium, magnesium, and chloride)

Diarrhea

Persistent diarrhea or vomiting may need hospitalization

Antibiotics

Not commonly indicated

and/or the symIndicated when the kind of bacteria is determined ptoms are severe

The sooner treatment begins, the better

Other Drug Therapies

Antitoxin to neutralize toxins from C. botulinum (only given within

the first 72 hours)

Amitriptyline to control the numbness and tingling from ciguatera

poisoning

Apomorphine or ipecac syrup to cause vomiting and help rid the

body of toxins

Atropine for mushroom poisoning

Diphenhydramine and cimetidine for fish poisoning

Mannitol for nerve-related symptoms of ciguatera poisoning H.W.

H.W.

H.W.

Encourage your people to:

Wash hands, utensils and food surfaces often

Keep raw foods separate from ready-to-eat foods

Cook foods to a safe temperature

Refrigerate or freeze perishable foods promptly

Defrost food safely

Throw it out when in doubt

REFERENCING GUIDLINEcopharm.uobaghdad.edu.iq/wp-content/uploads/sites/... · •Acetaminophen...

Documents

Transcript of REFERENCING GUIDLINEcopharm.uobaghdad.edu.iq/wp-content/uploads/sites/... · •Acetaminophen...